Prevalence, incidence, and trends of epilepsy among children and adolescents in Africa: a systematic review and meta-analysis

Background Epilepsy contributes to a significant disease burden in children and adolescents worldwide. The incidence of childhood epilepsy is threefold higher in low and middle income countries compared in high-income countries. Epilepsy is a serious neurological condition associated with stigma and discrimination, an impaired quality of life, and other mental health related problems. Objective This study is aimed to synthesize existing evidence and estimate the pooled prevalence and incidence of epilepsy in children and adolescents in Africa. Methods A comprehensive and systematic search of relevant databases was conducted. The quality of each study was assessed using the Newcastle-Ottawa Quality Assessment Scale adapted for meta-analysis. Two reviewers screened retrieved articles, conducted critical appraisals, and extracted the data. Heterogeneity between studies was assessed by visual inspection of forest plots and statistically using Cochran’s Q statistics and the I2 test. Publication bias was checked by visual inspection of funnel plots as well as statistically using Egger’s correlation and Begg’s regression tests. Finally, the pooled prevalence and incidence of childhood epilepsy were computed with 95% confidence intervals. Result In this review and meta-analysis 42 studies with 56 findings were included to compute the pooled prevalence of childhood epilepsy. On the other hand, 6 studies were included to estimate the combined incidence. The pooled prevalence of cumulative epilepsy was 17.3 per 1000 children. Whereas the pooled prevalence of active and lifetime epilepsy was 6.8 and 18.6 per 1000 children respectively. The pooled incidence of childhood epilepsy was 2.5 per 1000 children. Conclusion Nearly 1 in 50 children are suffering from epilepsy in Africa. However, little attention has been paid to the prevention and treatment of childhood epilepsy. Mass epilepsy screening, scaling up treatment coverage, and designing strict treatment follow up and monitoring mechanisms are recommended.


Introduction
Epilepsy is a chronic neurological condition that affects over 50 million people of all ages and sexes worldwide [1][2][3].The prevalence of epilepsy is disproportionately concentrated in low and middle-income countries (LMICs).The incidence of epilepsy is almost threefold higher in LMICs (139 per 100, 000) compared in high-income countries (HICs) (48.9 per 100, 000) [4][5][6].Moreover, premature mortality associated with epilepsy is significantly higher in LMIC compared in HICs.The high burden of epilepsy in LMICs is largely attributed to inadequate medical services, poor socioeconomic conditions, and traditional beliefs regarding the treatment of epilepsy [7].
Epilepsy contributes to a significant disease burden in children and adolescents worldwide.Globally, more than 11 million children aged less than 15 years have active epilepsy [8][9][10].In 2017, more than 291 million children aged less than 20 had epilepsy and intellectual disabilities, of which 95% lived in low and middle income countries [11].In addition, more than 90% of epileptic cases in Sub-Saharan countries have been reported in children and adolescents aged < 20 years [12,13].Similarly, majority of epileptic cases in Ethiopia are reported in children and young adolescents [14,15].
The highest incidence of epilepsy is reported during the early age of children and decline as age increases to adulthood [5,16,17].A study in Norway suggests that incidence of epilepsy was reported144 per 100, 000 person-years in the first year of life.It then dropped to 61 per 100, 000 person-years in children aged 1 to 4 years and 54 per 100, 000 person-years in children aged 5 to 10 years.The perinatal and neonatal complications as well as early childhood infection contributes to the high burden of epilepsy in the early age of children [16].
Epilepsy is caused by both modifiable and nonmodifiable risk factors.However, the causes are varied significantly between developing and developed countries.The main etiologies of epilepsy in developing countries are birth asphyxia, febrile seizures, perinatal and neonatal problems, and head related traumas.Whereas the common etiologies reported in developed countries are brain tumors, traumatic head injury, and cerebrovascular diseases [7,12,18].In addition, epilepsy is found to be higher in children with family history of seizure.More than 20% of childhood epilepsy is associated with genetic inheritance [19].Furthermore, parasitic infections like onchocerca volvulus, neurocysticercosis, and infection with plasmodium species are associated with increased rate of childhood epilepsy [20].
Epilepsy has a deadly impact on the lives of children and their family members.It is the leading cause of neurological impairment in children worldwide [21].Children with epilepsy experiences poor school performance and school dropout, traumas including head traumas and burns, stigma and discriminations, mental health problems, impaired cognitive development, and premature mortality [22,23].In addition, epilepsy causes serious psychosocial consequences among families members due to the belief that the condition is resulted from sorcery practiced by the society, a breach of traditional cultural taboos, bad luck, or punishment from God for wrong feat [3,24,25].
Although epilepsy has such enormous negative consequences on the lives of children and their families; little or no attention has been paid to the treatment and prevention of disease in Africa.Consequently, millions of children and their families are still suffering from epilepsy.Additionally, no conclusive studies have been conducted to show the burden of epilepsy among children in Africa.Therefore, the findings of this study provide more general and conclusive evidence that provides essential insights to the prevention and treatment of childhood epilepsy in the continent.

Design and protocol registration
A systematic review and meta-analysis of observational studies on childhood epilepsy were conducted in the African countries.The protocol for this review and meta-analysis was prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P-2015) statement [26].The protocol is registered at PROSPERO with the registration number CRD42022329754/www.crd.york.ac.uk/prospero.

Eligibility criteria
The inclusion criteria for this study were studies on epilepsy among children aged less than 18 years; studies conducted in the African countries; observational studies (case-control, cross-sectional, and cohort studies); studies reported the prevalence or incidence of epilepsy; and English language articles that have been published in peer-reviewed journals without restriction of publication date.Articles that were not fully accessed were excluded because of incomplete data.Additionally, case reports, conference reports, expert opinions and qualitative studies were excluded.

Search strategies
Systematic search of electronic databases MEDLINE/ PubMed, HINARI, Web of Science, SCOPUS, and African Journals online (AJOL), as well as other gray literature and online open-access institutional repositories were retrieved using different search strategies.In addition, manual searches were conducted to identify additional studies.Manual searches are supplemental approaches to database searches conducted by inputting specific search terms or conditions into a search system or interface [27].The searching terms were developed based on the research questions and study objectives.The following keywords were used in combination or in separation to find relevant articles in the African countries: Epilepsy/Seizure/Convulsion, and Magnitude/Epidemiology/Prevalence/Incidence, and Children/Adolescents/Pediatrics/Infants/ Neonates.

Study screening and selection
The Preferred Reporting Items for Systematic review and Meta-analyses (PRISMA-2015) diagram was used to screen retrieved studies and report the findings [28].A total of 2547 studies were retrieved through electronic databases, gray literature, and manual searches.All retrieved articles were imported to EndNote X8 reference managers and 960 articles were removed because of duplications.After excluding duplicate articles, the titles and abstract of 1587 articles were reviewed and 1234 were removed because of unrelated titles or outcomes not reported.The full text of 353 articles were reviewed which resulted in further exclusion of 311 articles.Finally, 42 articles with 56 epilepsy reports (unclassified, active, or lifetime epilepsy) were included (Fig. 1).

Quality assessment
The quality of each study was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) adapted for meta-analysis.Stars were assigned to evaluate study quality with 9-10 stars indicating "very good" quality, 7-8 stars "good" quality, 5-6 stars "satisfactory" quality, and 0-4 stars indicating "unsatisfactory" quality.Two authors (NA and GB) have conducted the quality appraisals and the average assessment scale of the two authors were used for the final decision.

Data extraction and management
Data was extracted using Microsoft Excel 2016 spreadsheet and the Joanna Briggs Institute (JBI) data extraction form for observational studies.Two authors (GB and KD) reviewed the included studies and extracted data from eligible articles.The third reviewer (NE) handled disagreements between the two authors and consensus was reached through discussion.

Heterogeneity
Heterogeneity was assessed using Cochran's Q statistics and the I 2 tests.A p-value < 0.10 of the Cochran's Q statistic and the I 2 test statistic of greater than 75% were declared to have significant statistical heterogeneity [29].Significant heterogeneity was observed between studies; consequently, subgroup analysis was conducted based on the types of epilepsy reported, study settings, and by the region of the country.However, non of these were the source of heterogeneity.

Publication bias
The possible risk of publication bias was examined by visual inspection of funnel plot and by the statistically by Begg's correlation and Egger's regression tests.The visual inspection of funnel plot showed significant publication bias with substantial asymmetry.Consequently, Begg's correlation and Egger's regression tests were performed.Egger's and Begg's statistical tests revealed significant publication bias with p-value of < 0.001 and p = 0.0034 respectively.Sensitivity analysis showed that individual studies have excessive influence on the overall estimate since the point estimate of omitted studies lies outside the confidence interval of the combined analysis.Due to the presence of a substantial publication bias, trim and fill analysis was performed which yields an unbiased estimate of effect size (Fig. 2).
The highest prevalence of childhood epilepsy was observed in neurological units of hospital-based studies in South Africa and Nigeria.In these studies more than half children who visited the neurological units had epilepsy [53,59].In addition, a higher prevalence of epilepsy was reported in parasitic endemic areas of Cameroon, the Republic of Sudan, South Sudan, and the Republic of Congo [45,55,61,64,65].Additionally, exposure to multiple parasites is associated with a higher rate of active convulsive epilepsy [71].
The pooled prevalence of epilepsy in the health institutions was 189 (95% CI: 155.7, 221.3) per 1000 children.Whereas, the pooled prevalence of epilepsy in high parasite endemic areas was 44 (95%CI: 35.6-53.2) per 1000 children.However, the pooled prevalence of epilepsy in the general population was 8 (95% CI: 7.3 Fig. 1 The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart to screen studies included in the review and meta-analysis to 9.2) per 1000 children (Fig. 5).Subgroup analysis was performed by region or location of the country.The highest prevalence of epilepsy was reported in Southern African countries (129.3/1000)followed by Central African countries (32.3/1000) and Northern African countries (24.1/1000 (Fig. 6).

Incidence of epilepsy
Six studies were included to estimate the pooled incidence of epilepsy in children and adolescents in Africa.The incidence of epilepsy varies significantly in the African countries.The highest incidence was reported in Tanzania (850 per 100,000) [72] and the lowest reported in Kenya (60/100,000) [41] and Nigeria (94/100,000) [73].The pooled incidence of epilepsy in children and adolescents was 250 per 100, 000 children (95%CI:180-320, I 2 : 97.94%, p < 0.001)(Fig.7).

Discussion
In this review and meta-analysis, the authors explored and integrate evidence available on childhood epilepsy in Africa.Through gathering and summarizing all available evidence on childhood epilepsy the authors have provided a more representative and reliable data regarding childhood epilepsy in the continent.The knowledge derived from this review and meta-analysis can be used as baseline data by policymakers, national and international organizations, researchers, and other stakeholders to design and implement strategies to control childhood epilepsy in Africa.
The prevalence of epilepsy varies significantly between and within countries in Africa.The prevalence rate ranges from 0.2/1000 in Senegal [30] to 510/1000 in South Africa [53] and 594/1000 in Nigeria [59].This variation could be attributed to the heterogeneity of methodology or differences in the definition of epilepsy between studies.The variation could also be due to the nature of reported epilepsies; lifetime, active, or cumulative epilepsies.In addition, the variation could be related to the settings in which the samples selected.In some studies, samples were selected from the general population which could better represent the population.However, in other studies, samples were selected from hospitals particularly in neurological units which increases the prevalence.Additionally, the inconsistencies might be related to the use of different epilepsy screening tools.
This study reveals that epilepsy remains a significant public health concern in Africa.One in fifty children in Africa are suffering from this preventable and treatable medical condition.This finding is supported by the global studies [11,74] and studies in developing countries [10,13,18].The reason could be children are vulnerable to perinatal and neonatal complications and early childhood infections which are risk factors of epilepsy [10,43].Moreover, the high endemicity of neuro-parasites in some African countries might contribute to the high burden of epilepsy in children and adolescents in Africa [71].
The prevalence of cumulative epilepsy was 17.3 per 1000 children (95% CI: 15.60-19.00).This   [12].The reason could be explained in terms of population differences where the current study involved children and adolescents, which increases the prevalence of epilepsy due to the neonatal and perinatal complications as well as early childhood infections.The prevalence of active epilepsy was 6.8 (95%CI: 5.7-8.00)per 1000 children.The finding is congruent with the systematic review and meta-analysis of international studies (6.38, 95% CI: 5.57-7.30)per 1000 persons [6].The high prevalence of active epilepsy in children and adolescents could be related to the poor treatment adherence or frequent exposure to epilepsy risk factors.The prevalence of lifetime epilepsy was 18.6 (95% CI: 12.6-24.5 ) per 1000 children.The finding was higher than the systematic review and meta-analysis of international studies (7.60, 95% CI 6.17-9.38)per 1000 children [6] and with similar estimate of the global burden of epilepsy [7].The reason could be partly explained in terms of the higher reported risk factors of epilepsy in Africa such as perinatal and neonatal infection, traumatic brain injury, and other central nervous system infections.In addition, the large treatment gap and poor treatment outcome contribute to the high burden of epilepsy in the African countries [17,58].
The incidence rate of epilepsy is highly varied across studies [41,72,73].The observed heterogeneity could be attributed to the incidence rate estimation where some studies estimated the incidence rate per year and others estimated in every two or three years.The pooled incidence of epilepsy was 250 (95%CI:180-320, I 2 : 97.94%, p < 0.001) per 100,000 children.The incidence was higher than global incidence of epilepsy (89.06, 95%CI; 31.68-98.01)[21], the meta-analysis of international studies (61.44, 95% CI 50.75-74.38)per 100,000 person-years [6], and a study in Norway (70, 95%CI: 64-75) [16].The reason could be explained by the different in the source populations at risk where the current study involves children and adolescents whereas the later study was on the general population.
The prevalence of epilepsy was 24 folds higher in institutional based studies compared to population based studies.The reason could be children in neurological units are complaints of neurological problems which increases the prevalence of epilepsy due to the higher epilepsy case load in these institutions.The higher prevalence of epilepsy in the health institutions reveals that emphasis should be given to mass epilepsy screening at the community level.
The pooled estimate of childhood epilepsy was higher in parasite endemic areas.This finding is supported by other studies in the continent [71,75].The reason could be neuro-parasites causes infection to the brain which then alter the electrical activity of the brain and causes epilepsy [71].Therefore, prevention and early treatment of parasitic infections such as malaria, neurocysticercosis, and onchocerca has an advantage to the control of childhood epilepsy.
This study reveals that the prevalence of epilepsy has been increasing over the last 30 years in children and adolescents.This could be due to the fact that the number of studies on epilepsy increases over time which could better investigate more epilepsy cases in the community.In addition, the increased prevalence may actually reflect better awareness and education around epilepsy due to increased efforts in the past decade.Thus, there may be both better recognition by providers as well as better health-seeking behaviors.The highest prevalence of epilepsy was reported between 2017 and 2022.The average rate of epilepsy in these years was 19.82 per 1000 children.The reason could be explained in terms of increased population crisis and its associated negative mental health consequences which might contribute to an increased burden of epilepsy.This suggests that more population-based epilepsy screening as well as escalating the prevention and treatment of epilepsy should be strengthened (Fig. 8).

Conclusion
Epilepsy has still contributed to a significant disease burden in children and adolescents in African.However, little or no attention has been paid to the prevention and control of the diseases.Mass epilepsy screening, escalating preventive and treatment measures, as well as regular treatment follow up and monitoring are recommended towards the control of childhood epilepsy.

Fig. 2 A
Fig. 2 A Funnel plot that includes both the observed studies and the imputed studies

Fig. 8 Fig. 7
Fig. 8 Trends of childhood epilepsy prevalence in Africa from 1992 to 2022 (n = number of study in the specified years)

Table 1
Characteristics of included studies the prevalence of epilepsy in African countries August 2023